LPA production, metabolism, and signaling. (a) LPA species are derived from membrane phospholipids. PLA removes a fatty acid chain from PC, PE, or PS converting them into lysophospholipids. Afterwards, ATX removes the head group from LPC < LPE < LPS and produces LPA. LPC can derive from cell membrane or circulating LPC bound to albumin. LPA can also be produced intracellularly by cPLA2 from LPC producing LPA and arachidonic acid. On the other hand, PLD can remove the head group from membrane phospholipids and produce PA. Then, sPLA2 removes a fatty acid chain producing LPA. Two enzymes metabolize LPA, LPP1 in the outer leaflet of the membrane hydrolyzes LPA into MAG, and LPAAT transfers an acyl chain to LPA in the inner leaflet of the membrane producing PA. (b) LPA signals through at least six GPCRS (LPA1–6
) that couple to different Gα
proteins to elicit activation of Rho, PLC, Ras, PI3K, and adenylyl cyclase (AC) and mediate diverse processes that are cell and context dependent. This figure is reproduced from Blaho and Hla [29
] (under the Creative Commons Attribution License/public domain).